Title: Methods of Studying The Nervous System
1Methods of Studying The Nervous System
2Outline
- Summary of Previous Lecture
- Methods of Visualizing the Living Human Brain
- a. Contrast X-rays
- b. Computerized Axial Tomography
- c. Magnetic Resonance Imaging
- d. Positron Emission Tomography
- e. Functional MRI
- f. Magnetoencephalography
- (3) Recording Psychophysiological Signals
- a. Scalp Electroencephalography
- b. Measures of Somatic Nervous System Activity
- c. Autonomic Nervous System Activity
3Methods of Visualizing the Living Human Brain
4Contrast X-rays
- To take an X-ray photograph of an object, a beam
of x-rays is passed through it onto a
photographic plate any part of the object that
absorbs X-rays differently than does the
surrounding medium will be distinguishable
5Contrast X-rays
- Standard X-rays cant be used for studying the
brain because the brain is composed of many
overlapping structures that all absorb X-rays to
about the same degree - Contrast X-rays solve this problem in some cases
a radio-opaque material is introduced into the
structure of interest to make it stand out from
the others on an X-ray photograph
6Contrast X-rays
- For example, in cerebral angiography a
radio-opaque dye is injected onto the carotoid
artery it reveals displacement or enlargement of
blood vessels
7Computerized Tomography(CT)
- Provides a 3-dimensional view of structure
- The X-ray gun and the X-ray detector rotate in
apposition around the brain at one level taking a
series of measurements from which an image of one
section is constructed this is repeated at
multiple levels - The CT-scan image of the brain is not high
spatial resolution
8Magnetic Resonance Imaging (MRI)
- It has highest spatial resolution
- The images are created from measurements of the
waves emitted by hydrogen atoms when they are
placed in a magnetic field - Its clarity stems from the fact that neural
structures differ considerably in their density
of hydrogen atoms
9Positron Emission Tomography (PET)
- A method of highlighting brain areas that are
active, rather than equally showing all brain
structures - The patient is injected with radio-active
2-deoxyglucose because 2-DG is structurally
similar to glucose, it is taken up by neurons as
if it were glucose (This is somewhat invasive,
although not as invasive as lesion surgery, etc.)
10Positron Emission Tomography (PET)
- More active neurons need more energy and take up
more 2-DG unlike glucose, 2-DG cannot be
metabolized by neurons and it accumulates in them
11Positron Emission Tomography (PET)
- The patient is injected with radio-active 2-DG
and then engages in the activity under study
(e.g., reading) while a PET scan of the brain is
being taken - The PET scan reveals on a series of images of
horizontal sections where radio-activity has
accumulated, and thus it indicates what areas
were particularly active during the test
12Functional Magnetic Resonance Imaging (fMRI)
- Allows brain activity to be measured by imaging
the increase in oxygen (blood flow) that occurs
to brain areas that are active - Surplus of blood occurs are active sites
13Functional Magnetic Resonance Imaging (fMRI)
- Its four advantages over PET include
- (1) nothing must be injected into the subject
- (2) one image provides structural and functional
information - (3) the spatial resolution is better
- (4) changes can be measured in real time
- (although, the temporal resolution is poor
compared to ERP)
14Magnetoencephalography (MEG)
- Measure brain activity in terms of changes in
magnetic fields measured on the surface of the
scalp
15Recording Psychophysiological Signals
16Scalp Electroencephalography (EEG)
- An EEG signal is measured through an array of
scalp electrodes - EEG waves reflect the sum total of all the
electrical events in the head (action potentials,
eye movements, blood flow, etc.) - thus, the EEG reveals little about the nature of
the underlying neural activity
17Scalp Electroencephalography (EEG)
- Its value lies in the fact that particular EEG
wave forms are associated with particular states
of consciousness generally low-amplitude, fast
EEG activity is associated with alert aroused
state and high-amplitude, slow EEG activity
(alpha waves) is associated with a relaxed but
awake state
18Scalp Electroencephalography (EEG)
- EEG can be used to study brain activity in real
time, in response to specific events. These are
called evoked potentials. - Usually many evoked potentials are used to
generate an averaged evoked potential in order to
reduce the noise of the background EEG activity
19Scalp Electroencephalography (EEG)
- A subset of evoked potentials are event-related
potentials, which are time-locked evoked
potentials, meaning that the EEG in response to
an event is always measured during a specific
interval of time - ERPs have good temporal resolution, but poor
spatial resolution
20Scalp Electroencephalography (EEG)
- EEG recording are a valuable diagnostic tool for
example the presence of high-amplitude spikes in
the EEG (i.e., epileptic spikes) is the primary
criterion for diagnosing epilepsy
21Measures of Somatic Nervous System Activity
- Muscle tension
- An electromygram (EMG) is the changing difference
in the voltage between two large electrodes
placed on the skin above a large muscle the
amplitude of EMG signals indicates the combined
level of tension in the underlying muscle - The raw signals are usually integrated so that
the data are easier to work with the height of
the curve of integrated EMG activity indicates
the number of spikes on the EMG signal per unit
of time
22Measures of Somatic Nervous System Activity
- Eye movement
- in an electrooculogram (EOG) eye movements are
recorded by placing four electrodes around the
eye the signals result from the fact that the
front of the eye is more positively charged than
the back - The direction of movement can be inferred from
the relation between the activity recorded on two
channels (1) above vs. below and (2) left vs.
right
23Autonomic Nervous System Activity
- Skin conductance
- Skin conductance level (SCL) is the general level
of skin conductance associated with a particular
situation - A skin conductance response (SCR) is a rapid
change in skin conductance in response to a
particular event one application is the lie
detector test - (break)
24Websites
- A Primer for CAT and MRI
- http//www.med.harvard.edu/AANLIB/hms1.html
- The Electroencephalogram
- http//www.medfak.uu.se/fysiologi/lectures/EEG.htm
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25Methods of Studying The Nervous System
26Outline
- (1) Invasive Physiological and Pharmacological
Methods - a. Stereotaxic Surgery
- b. Lesion Methods
- c. Electrical Stimulation
- d. Electrical Recording Methods
- e. Pharmacological Methods
- (2) Genetic Engineering
- a. Knockouts
- b. Gene replacement
27Invasive Physiological and Pharmacological Methods
- In most cases, laboratory animals serve as the
subjects when invasive procedures are required to
directly manipulate or measure the brain
28Stereotaxic Surgery
- The first step in may invasive biopsychology
experiments is stereotaxic surgery it allows
accurate placement of lesions, probes,
electrodes, and other devices into the brain
29Stereotaxic Surgery
- The method employs a stereotaxic atlas and a
stereotaxic instrument (head holder and electrode
holder) - The reference point is often bregma (the point
where two main plates of the rat skull naturally
fuse together)
30Lesion Methods
- The aspiration method is often used to remove
cortical tissue - The radio-frequency electrolytic lesion is the
most common subcortical lesion the tissue is
destroyed by the heat of the current
31Lesion Methods
- Small knife cuts are often used for severing
tracts - Cryogenic blockade is like a reversible lesion
the tissue is temporarily cooled to the point
that all neural activity in the vicinity of the
probe stops it produces little permanent damage
32Lesion Methods
- Lesion studies must be interpreted with caution
a lesion inevitably damages structures other than
the one that the surgeon targeted, and lesions
seldom completely remove a structure that is
targeted
33Electrical Stimulation
- The effects of electrical stimulation are often
opposite to those of a lesion to the same brain
site - Electrical stimulation research is done prior to
any lesioning
34Electrical Recording Methods
- Intracellular unit recording
- Measures changes in the membrane potential of a
neuron over time it requires a microelectrode
positioned inside a neuron - It is next to impossible to record
intracellularly in a freely moving animal because
it is difficult to keep the microelectrode inside
the neuron
35Electrical Recording Methods
- Extracellular unit recording
- A microelectrode is positioned near a neuron
- The signal is a series of spikes each spike
indicates an action potential from a nearby
neuron spikes of the same amplitude are assumed
to come from the same neuron
36Electrical Recording Methods
- Multiple unit recording
- Multiple unit recording provides an indication of
the rate of firing of many neurons in the general
vicinity of the electrode tip - An electrode larger than a microelectrode picks
up the action potentials from many nearby neurons - The signal is integrated so that the height of
the curve indicates the number of action
potentials in the vicinity per unit of time
37Electrical Recording Methods
- Invasive EEG recording
- Implanted electrodes are used to record EEG in
laboratory animals because the scalp electrode do
not allow as clear or finite position recording
38Pharmacological Methods
39Pharmacological Methods
- Routes of drug administration include
intragastrically (stomach), intraperitonally
(abdomen), intramuscularly, subcutaneuously, or
intravenously - These peripheral routes all suffer from th fact
that many drugs cannot pass the blood-brain
barrier - This problem can be overcome administering drug
via stereotaxically positioned cerebral cannula
(microinjection of drugs directly into brain
tissue)
40Pharmacological Methods
- Sometimes, drugs can be injected into the brain
that produce chemical lesions that are more
selective than electrical lesion might be for
example, 6-OHDA is a neurotoxin that selectively
destroys dopaminergic and noradrenergic neurons
in the vicinity of the injection site
41Locating Neurotransmitters and Receptors in the
Brain
- Immunocytochemistry begins by injecting antigens
(foreign proteins) into an animal such that the
animal will create and bind antibodies to the
antigen to remove or destroy it
42Locating Neurotransmitters and Receptors in the
Brain
- Antibodies for the most of the brains peptide
neurotransmitters and receptors have been
created these can be labeled with a dye or
radioactive element and then used to identify
specific neuroproteins in slices of brain tissue
43Locating Neurotransmitters and Receptors in the
Brain
- In situ hybridization also allows peptides and
proteins in the brain to be located labeled
hybrid RNA strands with a base sequence
complementary to the mRNA for synthesizing the
target neuroprotein - The hybrid RNA binds to the complementary mRNA in
the target cells and allows the target
neuroproteinss location to be marked
44Genetic Engineering
45Gene Knockout Techniques
- Involve the creation of organisms that lack a
specific gene any measurable neural or
behavioral anomalies are then noted
46Gene Knockout Techniques
- PROBLEMS
- Most behaviors are determined by multiple genes
- Eliminating one gene usually alters the
expression of other genes - Gene expression dependent upon experience, which
may be altered by the absence of the missing gene
47Gene Replacement Techniques
- Involves the replacement of one gene with
another useful implications for the treatment of
genetically related diseases - Sometimes, genetic information from a different
species is implanted, creating a transgenic
subject
48Website
- In vivo Microdialysis
- http//www.microdialysis.se/techniqu.htm